Tears which protect and nourish the cornea are secreted by several orbital glands. One of these, the lacrimal gland, contributes 60-80% of overflow tears stimulated by the secretagogue pilocarpine. Although the lacrimal gland contributes a major portion of overflow tears, the mechanism of its electrolyte and water secretion has not been well characterized. Thus the aim of this project is to investigate the mechanism of cholinergically-induced electrolyte and water secretion by determining the role of Na ion and Cl minus coupled transport in fluid secretion by the in vivo perfused rabbit lacrimal gland. The lacrimal gland also secretes proteins, which in the rabbit have not yet been identified. The mechanism of protein secretion and its relationship to electrolyte and water secretion have not been extensively investigated. Thus a second aim of the present study is to determine how closely coupled the control of protein secretion is to the control of electrolyte and water secretion by using the in vivo perfused rabbit and in vitro perifused rat exorbital lacrimal glands. The mechanisms which control protein secretion can then be further investigated by physiological and biochemical techniques. A final aim of this project is to determine whether putative secretagogues such as cholecystokinin, bombesin, physalaemin, vasoactive intestinal polypeptide and cholera toxin affect lacrimal gland electrolyte and water and/or protein secretion. These secretagogues affect secretion from other exocrine glands such as salivary gland and pancreas. In fact, the pancreas has distinct cell receptors for these secretogogues, which may provide nonautonomic nervous system control of secretion. Both the in vivo perfused rabbit and the in vitro perifused rat exorbital lacrimal gland will be used for these studies. Description of lacrimal gland secretion will provide a framework for investigation of orbital gland dysfunction which occurs in diseases affecting tear production.